Paul K. Crane, MD, MPH

I am a general internist on the faculty at the University of Washington. I attend on the medicine wards at Harborview Medical Center anywhere from 4 to 8 weeks per year. The rest of the time I do research.

My initial niche was in measurement in general and psychometrics in particular as applied to medical settings. Psychometrics is the statistical machinery with which scores are generated from test items. Psychometrics is very advanced in educational testing settings, but in medicine we have been slow to move beyond approaches that have been superseded for half a century in educational testing. At the same time, tests used in medical settings have particular characteristics that are distinct from educational testing. While educational testing companies employ legions of test item developers to continually renew test content, in medicine we tend to develop the test and re-use it as is. Furthermore, while in educational settings items for high stakes tests are always carefully vetted before they are used to generate scores for people, typically in medicine items receive less attention before they are used very widely, resulting in important challenges for valid inference if there are measurement issues such as differential item functioning (DIF).

My substantive research has focused on the use of psychometric tests in medical settings. In particular, I have focused on patient reported outcomes through the PROMIS initiative, and on cognition. Work on cognition led me to the field of Alzheimer's research, and I have been involved with the Adult Changes in Thought (ACT) study since my fellowship in 2002. I helped to write the Electronic Medical Records and Genomics (eMERGE) proposal from Group Health and the University of Washington; eMERGE included funds for genotyping samples from some 2400 ACT participants. We contributed those data to the Alzheimer's Disease Genetics Consortium (ADGC), which has also genotyped samples from an additional 400 participants. I serve as ACT's liaison to the ADGC. My group has been involved with several ADGC projects, including leading or co-leading groups on pathway analyses, gene-wide approaches, and association studies of the rate of cognitive decline among people with Alzheimer's disease.

I served as PI of a successful R01 in which we applied psychometric methods to data from the Alzheimer's Disease Neuroimaging Initiative. We published 35 papers in 5 years, including important papers describing our successful development of a memory composite score (ADNI-Mem), an executive functioning composite score (ADNI-EF), and an extension of the Alzheimer's Disease Assessment Schedule for Cognition (the ADAS-Cog) to add additional executive functioning content; we called our extension the ADAS-Cog-Plus. We used these scores to evaluate MRI and PET correlates of memory and executive functioning among people with normal cognition, mild cognitive impairment, and Alzheimer's disease. We improved upon a great idea by Dickerson and Wolk to investigate the difference between memory and executive functioning among people with early Alzheimer's disease. At one extreme of that distribution are people with relatively intact memory but profoundly impaired executive functioning, a clinical subgroup known as dysexecutive, frontal variant, or executive prominent Alzheimer's disease. We have published on genetic correlates of this subgroup. We also used imaging and cognitive data to define a resilience phenotype, and have published on the genetics of resilience.

CURRENT PROJECTS

Development and use of network infrastructure for high-throughput GWA studies

This project will continue the efforts of the Group Health/University of Washington eMERGE collaboration to expand the library of phenotypes derived from electronic medical records; advance the integration of genome-scale data into clinical practice; and broaden the impact of eMERGE through new collaborations.

Role: Co-Investigator.

Alzheimer's Disease Patient Registry (ADPR)

The Adult Changes of Thought (ACT) study's goals are to advance understanding of factors associated with late life brain outcomes of dementia, cognitive decline, and fixed and frozen findings at autopsy. (Wrote the majority of the grant application.)

Role: PI of UW subcontract.

Longitudinal Effect of Anticholinergic Polypharmacy on Dementia and Neuropathology

The goals of this project are to evaluate the validity of Patient Reported Outcome (PRO) Measurement Information System (PROMIS) scales for patients with HIV, and to integrate PRO assessment into routine clinical care. (Wrote the majority of the grant application.)